A tumor–immune balance index from stem-like circulating tumor cells is associated with outcomes after yttrium-90 radioembolization for hepatocellular carcinoma

Outcomes after yttrium-90 (Y-90) transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) remain heterogeneous, and blood-based biomarkers that capture dissemination biology are limited. We hypothesized that risk after TARE is governed by the balance between circulating tumor burden and host lymphocyte-mediated immune surveillance. In a prospective pilot cohort of 25 patients with unresectable HCC, we quantified total circulating tumor cells (CTCs; EpCAM + CD45 − ) and a stem-like subset (EpCAM + CD45 − CD44 + CD90 + ) by multiparametric flow cytometry and derived lymphocyte-normalized indices. Absolute total and stem-like CTC counts showed weak and imprecisely estimated relationships with tumor burden and showed limited ability to stratify progression-free survival (PFS). In contrast, the stem-like CTC-to-lymphocyte ratio, termed the Tumor–Immune Balance Index (TIBI), showed stronger apparent prognostic separation in exploratory analyses, and a combined CLR/TIBI schema identified a particularly high-risk group. Peripheral and hepatic venous sampling showed strong concordance, supporting peripheral blood as a practical sampling alternative. These findings support an exploratory, research-stage tumor–immune balance framework for risk stratification after radioembolization and provide a rationale for validation of CTC/lymphocyte-based biomarkers in contemporary HCC cohorts.